Pharmaceutical compositions comprising immuno suppressives, e.g. corticosteroids such as prednisolone or budesonide are well known for the treatment of hepatic diseases (Danielsson et al., Aliment. Pharmacol. Ther., 1994, 8, 585-590). Different in many aspects from other hepatic diseases, however, are, cholestatic diseases such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AC). It was the general belief in the art that the therapy with such immuno suppressives is not promising for the treatment of cholestatic diseases.
In particular, there were controlled clinical investigations whether prednisolone can be used for the treatment of PBC (Mitchison et al., Hepatology, 1989, 4, 420-429; Mitchison et al., Journal of Hepatology, 1992, 15, 336-344), however, the therapy with prednisolone is controversially discussed. The activity of prednisolone is not without doubt and, furthermore, severe side effects were observed. For this reason, up to now a therapy of PBC, PSC and AC with glucocorticoids was not considered being helpful (Paumgartner & Beuers, In: Falk Symposium 87, Acute and chronic liver diseases, 1996, 96-106; Rasenack and Gerok in Hepatologie (Ed. Gerok & Blum), 1995, page 435 and 439; Praktische Gastroenterologie, (Ed. Layer et al.), 1996, 397-398).
Therefore, for the treatment of cholestatic liver diseases there was up to now no alternative to a therapy with ursodeoxycholic acid which may not completely heal the disease but impressively alleviates the symptoms of the disease and improves the laboratory values (The new England Journal of Medicine, 1991, 1548; Seminars in Liver Disease, Volume 11, No. 1, 1991, 56; Gastroenterology 97, 1989, 1268; Internist, 35, 1994, 1147 and Journal of Hepatology, 21, 1994, 624-633).
Despite the fact that treatment with ursodeoxycholic acid alleviates the symptoms of the cholestatic liver diseases to some degree, there is still need in the art for further pharmaceutical compositions and methods for improving the treatment of cholestatic liver diseases, in particular of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AC).